Signaling lymphocytic activation molecule family 8 disrupts epithelial barrier in chronic rhinosinusitis with nasal polyps through M1 macrophage polarization

IF 5.8 2区医学 Q1 ALLERGY

Annals of Allergy Asthma & Immunology Pub Date : 2025-04-01 DOI:10.1016/j.anai.2025.01.020

Danyang Li MD, Longgang Yu MD, Jiajia Zi MM, Xiaoyun Du MD, Xudong Yan MD, Han Chen MD, Lin Wang MM, Chunge Zheng MD, Guangyi Wang MM, Jisheng Zhang MD, Yan Jiang MD

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引用次数: 0

Abstract

Background

Recent studies reveal that M1 macrophages accumulate predominantly in noneosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP). However, the precise mechanisms regulating M1 macrophages and their impact on the epithelial barrier remain unclear.

Objective

To investigate the expression and regulatory role of signaling lymphocytic activation molecule family (SLAMF)8, a molecule exclusively expressed in myeloid cells, in M1 macrophage polarization and its potential contribution to neCRSwNP development.

Methods

We evaluated SLAMF8 expression and its correlation with clinical variables using real-time quantitative polymerase chain reaction and Western blot in sinonasal mucosa samples from CRSwNP and control subjects. Immunofluorescence staining confirmed the co-expression of SLAMF8 with macrophages. After SLAMF8 knockdown, we explored the influence on macrophage M1 polarization and the effect on epithelial-mesenchymal transition (EMT) process and tight junction integrity in epithelial cells through an indirect co-culture system of M1 macrophages with human nasal epithelial cells.

Results

SLAMF8 was highly expressed on M1 macrophages in polyp tissues, notably in neCRSwNP, and correlated with disease severity indices only in neCRSwNP. SLAMF8 knockdown in THP-1 cells reduced M1 macrophage markers (CD86, iNOS, and NLRP3) and decreased secretion of inflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha). Co-culture with M1 macrophage supernatant after SLAMF8 knockdown enhanced epithelial viability, reduced EMT and apoptosis, and up-regulated tight junction markers, occludin and claudin-4, in nasal epithelial cells.

Conclusion

SLAMF8 elevation correlates with the EMT, epithelial tight junction, and disease severity in neCRSwNP. SLAMF8 up-regulation promotes M1 macrophage polarization, which facilitates EMT and impairs nasal epithelial barrier function. SLAMF8 may represent a novel therapeutic target for neCRSwNP.

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SLAMF8通过M1巨噬细胞极化破坏慢性鼻窦炎伴鼻息肉的上皮屏障。

背景：最近的研究表明，M1巨噬细胞主要积聚在非嗜酸性慢性鼻窦炎伴鼻息肉（neCRSwNP）中。然而，调节M1巨噬细胞的确切机制及其对上皮屏障的影响尚不清楚。目的：研究骨髓细胞中表达的分子SLAMF8在M1巨噬细胞极化中的表达和调控作用及其对neCRSwNP发展的潜在贡献。方法：采用实时定量聚合酶链反应和Western blot技术对CRSwNP和对照组鼻黏膜标本中SLAMF8的表达及其与临床变量的相关性进行分析。免疫荧光染色证实SLAMF8与巨噬细胞共表达。在SLAMF8基因敲除后，我们通过M1巨噬细胞与人鼻上皮细胞的间接共培养系统，探讨了对巨噬细胞M1极化的影响，以及对上皮细胞上皮间质转化（epithelial-mesenchymal transition， EMT）过程和紧密连接完整性的影响。结果：SLAMF8在息肉组织M1巨噬细胞上高表达，在neCRSwNP中表达最为明显，且仅在neCRSwNP中与疾病严重程度指标相关。THP-1细胞中SLAMF8的敲除降低了M1巨噬细胞标志物（CD86、iNOS和NLRP3），减少了炎症细胞因子（IL-1β、IL-6和TNF-α）的分泌。SLAMF8敲除后与M1巨噬细胞上清共培养可增强鼻上皮细胞活力，减少EMT和细胞凋亡，上调鼻上皮细胞紧密连接标志物Occludin和Claudin-4。结论：在neCRSwNP中，SLAMF8升高与EMT、上皮紧密连接和疾病严重程度相关。SLAMF8上调促进M1巨噬细胞极化，从而促进EMT，损害鼻上皮屏障功能。SLAMF8可能是neCRSwNP的一个新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Allergy Asthma & Immunology 医学-过敏

CiteScore

6.50

自引率

6.80%

发文量

437

审稿时长

33 days

期刊介绍： Annals of Allergy, Asthma & Immunology is a scholarly medical journal published monthly by the American College of Allergy, Asthma & Immunology. The purpose of Annals is to serve as an objective evidence-based forum for the allergy/immunology specialist to keep up to date on current clinical science (both research and practice-based) in the fields of allergy, asthma, and immunology. The emphasis of the journal will be to provide clinical and research information that is readily applicable to both the clinician and the researcher. Each issue of the Annals shall also provide opportunities to participate in accredited continuing medical education activities to enhance overall clinical proficiency.